The major objectives of this project are (1) to establish the structural parameters of collagen involved in interaction with platelets by preparation and by detailed chemical characterization of the genetically distinct types of collagen in human aorta, and by the thorough examination of biochemical events associated with the interaction, and (2) to extend these studies to the examination of arteriosclerotic aorta for possible alterations in the pertinent structural parameters of collagen. At the present time, the salient characteristics and functional groups of collagen involved in this interaction are not well understood and are controversial. We plan, therefore, to isolate and purify each of the genetically distinct types of collagen, the type-specific alpha chains, and the CNBr peptides from human aorta. Each of the preparations will be examined for its interaction with platelets by aggregometry, by studying the effects on serotonin release reaction, the platelet content of cyclic nucleotides, the activity of guanylate and adenylate cyclases and protein kinases of platelets, and specific binding by isolated platelet membranes. Contrary to the generally held concept that only the particulate forms of native collagen is capable of mediating platelet aggregation, we have clearly shown that a small soluble peptide derived from collagen also interacts with platelet membranes. This allows an in-depth investigation of the processes involved in the phenomena at the molecular level. The recent discovery of the existence of several genetically distinct types of collagen in various connective tissues, and of alterations in the tissue distribution of the types of collagen in several human disorders of connective tissue, further emphasizes the need for definitive information on the nature of collagen present in vessel walls, possible alterations in diseased states, the respective role played by each type of collagen in interaction with platelets, and the precise definition of the structures involved.